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Published on: February 23, 2014
Mobile elements and chromosomal changes associated with MLS resistance phenotypes of invasive pneumococci recovered
Paulina A Hawkins1, Sopio Chochua, Delois Jackson
11 Hubert Department of Global Health, Rollins School of Public Health, Emory University , Atlanta, Georgia .
Abstract:
Pneumococcal macrolide resistance is usually expressed as one of two phenotypes: the M phenotype conferred by the mef gene or the MLSB phenotype caused by modification of ribosomal targets, most commonly mediated by an erm methylase. Target-site modification leading to antibiotic resistance can also occur due to sequence mutations within the 23S rRNA or the L4 and L22 riboproteins. We screened 4,535 invasive isolates resistant to erythromycin and 18 invasive isolates nonsusceptible to quinupristin-dalfopristin (Q-D) to deduce the potential mechanisms involved. Of 4,535 erythromycin-resistant isolates, 66.2% were polymerase chain reaction (PCR)-positive for mef alone, 17.8% for ermB alone, and 15.1% for both mef and ermB. Thirty-seven isolates (0.9%) were PCR negative for both determinants. Of these, 3 were positive for ermA (subclass ermTR) and 25 had chromosomal mutations. No chromosomal mutations (in 23S rRNA, rplD, or rplV) nor any of the macrolides/lincosamides/streptogramin (MLS) resistance genes screened for (ermT, ermA, cfr, lsaC, and vgaA) were found in the remaining nine isolates. Of 18 Q-D nonsusceptible isolates, 14 had chromosomal mutations and one carried both mef and ermB; no chromosomal mutations or other resistance genes were found in 3 isolates. Overall, we found 28 mutations, 13 of which have not been previously described in Streptococcus pneumoniae. The role of these mutations remains to be confirmed by transformation assays.
Insights
Pneumococcal resistance to macrolide antibiotics is primarily due to mef genes or erm methylases. This study identified novel ribosomal mutations in Streptococcus pneumoniae, expanding our understanding of antibiotic resistance mechanisms.
Area of Science:
- Microbiology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Pneumococcal macrolide resistance presents as M phenotype (mef gene) or MLSB phenotype (erm methylase).
- Antibiotic resistance can also arise from ribosomal target mutations (23S rRNA, L4, L22 riboproteins).
- Understanding resistance mechanisms is crucial for effective treatment of invasive pneumococcal disease.
Purpose of the Study:
- To investigate the mechanisms of macrolide and quinupristin-dalfopristin resistance in invasive Streptococcus pneumoniae isolates.
- To identify novel genetic determinants contributing to antibiotic resistance in pneumococci.
Main Methods:
- Screening of 4,535 erythromycin-resistant and 18 quinupristin-dalfopristin-nonsusceptible invasive pneumococcal isolates.
- Polymerase chain reaction (PCR) to detect known resistance genes (mef, ermB, ermA, ermT, cfr, lsaC, vgaA).
- Analysis of chromosomal mutations in 23S rRNA, rplD, and rplV genes.
Main Results:
- Prevalence of resistance genes: mef (66.2%), ermB (17.8%), both mef and ermB (15.1%) in erythromycin-resistant isolates.
- Chromosomal mutations were identified in 25 erythromycin-resistant isolates and 14 quinupristin-dalfopristin-nonsusceptible isolates.
- A total of 28 mutations were found, with 13 previously undescribed in Streptococcus pneumoniae.
Conclusions:
- The study highlights the diverse genetic basis of macrolide and quinupristin-dalfopristin resistance in pneumococci.
- Novel chromosomal mutations contribute significantly to antibiotic resistance, requiring further investigation.
- Transformation assays are needed to confirm the role of newly identified mutations in resistance.
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